Electroporation by subnanosecond pulses

Semenov, Iurii; Xiao, Shu; Pakhomov, Andrei G.

doi:10.1016/j.bbrep.2016.05.002

Cited by 22 publications

(11 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another hallmark of electroporation is a persistent loss of the resting membrane potential due to leak currents 24 , 37 . In various types of cells, repair of the membrane and the restoration of the resting potential takes from tens of seconds to minutes 10 , 17 , 24 , 37 , 38 , consistent with data for other types of membrane injuries 39 . Then, repeated electroporating pulses which do not allow sufficient interval for the membrane repair would lead to cumulative damage and the complete loss of both the resting potential and fiber excitability.…”

Section: Resultssupporting

confidence: 85%

Damage-free peripheral nerve stimulation by 12-ns pulsed electric field

Casciola

Xiao

Pakhomov

2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Modern technologies enable deep tissue focusing of nanosecond pulsed electric field (nsPEF) for non-invasive nerve and muscle stimulation. However, it is not known if PEF orders of magnitude shorter than the activation time of voltage-gated sodium channels (VGSC) would evoke action potentials (APs). One plausible scenario requires the loss of membrane integrity (electroporation) and resulting depolarization as an intermediate step. We report, for the first time, that the excitation of a peripheral nerve can be accomplished by 12-ns PEF without electroporation. 12-ns stimuli at 4.1–11 kV (3.3–8.8 kV/cm) evoked APs similarly to conventional stimuli (100–250 μs, 1–5 V, 103–515 V/m), except for having higher selectivity for the faster nerve fibers. Nerves sustained repeated tetanic stimulations (50 Hz or 100 Hz for 1 min) alternately by 12-ns PEF and by conventional pulses. Such tetani caused a modest AP decrease, to a similar extent for both types of stimuli. Nerve refractory properties were not affected. The lack of cumulative damages even from tens of thousands of 12-ns stimuli and the similarities with the conventional stimulation prove VGSC activation by nsPEF without nerve membrane damage.

show abstract

Section: Resultssupporting

confidence: 85%

Damage-free peripheral nerve stimulation by 12-ns pulsed electric field

Casciola

Xiao

Pakhomov

2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Persistent loss of the resting MP for tens of seconds and minutes is a well-known manifestation of cell membrane permeabilization (electroporation) by nsPEF[24, 25], but the time course of the depolarization and MP recovery have not been studied.…”

Section: Resultsmentioning

confidence: 99%

“…These numbers are promising for neurostimulation with nsPEF, but they have not been independently confirmed. The results of Cooper’s group are in stark contrast with other studies which utilized stimuli of comparable duration and reported 20- to 100-fold higher thresholds[24, 27, 28, 35, 36, 38, 40, 42]. Admittedly, all these other studies used endpoints other than AP generation in primary neurons, which could contribute to the inconsistency and emphasized the need to focus exactly on the AP induction in neurons.…”

Section: Introductionmentioning

confidence: 86%

“…Nanopores display complex conductive properties, including voltage and current sensitivity, inward rectification, and ion selectivity, which have not been fully explained[11, 12, 24]. The formation of nanopores, due to their extraordinary long life span (seconds to minutes) affects practically all aspects of cell physiology, from causing a persistent depolarization of the resting membrane potential (MP)[25, 26], activation of Ca 2+ [27, 28] and phosphoinositide signaling[3, 29] after a mild permeabilization, to cell volume changes and apoptotic or necrotic cell death[7, 30–32] after more intense treatments.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neuronal excitation and permeabilization by 200-ns pulsed electric field: An optical membrane potential study with FluoVolt dye

Pakhomov

Semenov

Casciola

et al. 2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

Self Cite

View full text Add to dashboard Cite

Electric field pulses of nano- and picosecond duration are a novel modality for neurostimulation, activation of Ca2+ signaling, and tissue ablation. However it is not known how such brief pulses activate voltage-gated ion channels. We studied excitation and electroporation of hippocampal neurons by 200-ns pulsed electric field (nsPEF), by means of time-lapse imaging of the optical membrane potential (OMP) with FluoVolt dye. Electroporation abruptly shifted OMP to a more depolarized level, which was reached within <1 ms. The OMP recovery started rapidly (τ = 8–12 ms) but gradually slowed down (to τ > 10 s), so cells remained above the resting OMP level for at least 20–30 s. Activation of voltage-gated sodium channels (VGSC) enhanced the depolarizing effect of electroporation, resulting in an additional tetrodotoxin-sensitive OMP peak in 4–5 ms after nsPEF. Omitting Ca2+ in the extracellular solution did not reduce the depolarization, suggesting no contribution of voltage-gated calcium channels (VGCC). In 40% of neurons, nsPEF triggered a single action potential (AP), with the median threshold of 3 kV/cm (range: 1.9–4 kV/cm); no APs could be evoked by stimuli below the electroporation threshold (1.5–1.9 kV/cm). VGSC opening could already be detected in 0.5 ms after nsPEF, which is too fast to be mediated by the depolarizing effect of electroporation. The overlap of electroporation and AP thresholds does not necessarily reflect the causal relation, but suggests a low potency of nsPEF, as compared to conventional electrostimulation, for VGSC activation and AP induction.

show abstract

“…In addition, the cell permeabilization can also be caused by pulsed electric fields. The electric field at a distance of ~100 μ m from TPE was found to be 90 kV/cm, which is lower than 200 kV/cm, the field required to cause cell permeabilization in single-shot experiments previously reported for 0.5 ns pulses [5, 7]. But the temperature rise and intermittent jet pressure and microstreaming forces may likely assist in the membrane permeabilization.…”

Section: Discussionmentioning

confidence: 72%

Cell Fragmentation and Permeabilization by a 1 ns Pulse Driven Triple-Point Electrode

Yang

Cho

et al. 2018

BioMed Research International

Self Cite

View full text Add to dashboard Cite

Ultrashort electric pulses (ns-ps) are useful in gaining understanding as to how pulsed electric fields act upon biological cells, but the electric field intensity to induce biological responses is typically higher than longer pulses and therefore a high voltage ultrashort pulse generator is required. To deliver 1 ns pulses with sufficient electric field but at a relatively low voltage, we used a glass-encapsulated tungsten wire triple-point electrode (TPE) at the interface among glass, tungsten wire, and water when it is immersed in water. A high electric field (2 MV/cm) can be created when pulses are applied. However, such a high electric field was found to cause bubble emission and temperature rise in the water near the electrode. They can be attributed to Joule heating near the electrode. Adherent cells on a cover slip treated by the combination of these stimuli showed two major effects: (1) cells in a crater (<100 μm from electrode) were fragmented and the debris was blown away. The principal mechanism for the damage is presumed to be shear forces due to bubble collapse; and (2) cells in the periphery of the crater were permeabilized, which was due to the combination of bubble movement and microstreaming as well as pulsed electric fields. These results show that ultrashort electric fields assisted by microbubbles can cause significant cell response and therefore a triple-point electrode is a useful ablation tool for applications that require submillimeter precision.

show abstract

Electroporation by subnanosecond pulses

Cited by 22 publications

References 33 publications

Damage-free peripheral nerve stimulation by 12-ns pulsed electric field

Damage-free peripheral nerve stimulation by 12-ns pulsed electric field

Neuronal excitation and permeabilization by 200-ns pulsed electric field: An optical membrane potential study with FluoVolt dye

Cell Fragmentation and Permeabilization by a 1 ns Pulse Driven Triple-Point Electrode

Contact Info

Product

Resources

About